Implementing barriers for controlled environments during sample processing and detection

Inventors

Beckett, Nathan • Caswell, Nathan

Assignees

Ultima Genomics Inc

Abstract

Provided herein are methods for processing and/or detecting a sample. A method can comprise providing a barrier between a first region and a second region, wherein the first region comprises the sample, wherein the barrier maintains the first region at a first atmosphere that is different than a second atmosphere of the second region, wherein a portion of the barrier comprises a fluid in coherent motion; and using a detector at least partially contained in the first region to detect one or more signals from the sample while the first region is maintained at the first atmosphere that is different than the second atmosphere of the second region. The portion of the barrier comprising fluid may have a pressure lower than the first atmosphere, the second atmosphere, or both.

Core Innovation

A system processes or analyzes an analyte by immobilizing the analyte adjacent to a substrate in a chamber, where a lid is disposed adjacent to and not in mechanical contact with the chamber. An environmental unit maintains a first local environment and a second local environment within the internal region while the lid is not in mechanical contact with the chamber and during movement of the substrate within the chamber. The first local environment is disposed above the second local environment and at or in proximity to the lid, while the second local environment is disposed at or near a surface of the substrate.

The environmental unit maintains the first local environment at a first temperature or first temperature range and maintains the second local environment at a second temperature or second temperature range, with the first temperature or first temperature range higher than the second temperature or second temperature range. The chamber internal region can further include a third local environment at or near a surface of the chamber bottom, in which a body of liquid generates vapor at a third temperature or third temperature range between the first and second temperature or ranges. The system can further constrain the internal region using a relative humidity greater than 90%.

The described systems integrate detection and relative motion concepts with the environmental separation. A detection unit can include an optical imaging objective at least partially immersed in an immersion fluid that contacts the substrate in the internal region, while another portion of the optical imaging objective is located in an external region outside the chamber. Movement of the substrate can include rotation relative to the chamber, and bulk fluid motion can provide a partial vacuum in a location between the chamber and the lid.

The document further describes sample-processing and detection concepts using multiple independently controlled local environments and scalable chamber designs with fluid-tight interfaces between detector and operating units. The overall system concept supports scanning and imaging while maintaining very high relative humidity while reducing condensation, corrosion/fouling, and contamination/ingress. Biological application examples include sequencing-by-synthesis with imaging and signal processing, including a parametric model with phasing/lead-lag and handling signal loss.

Claims Coverage

The independent claim specifies an analyte processing/analyzing system with a chamber and lid that are not mechanically coupled, and with an environmental unit that maintains two different local environments during substrate movement. The claim set also covers dependent refinements that add a third localized environment, a relative humidity constraint, an immersion-based imaging detection configuration, and specific relative substrate and fluid-motion behaviors, including partial vacuum.

Across the claim set, the core coverage centers on maintaining lid-proximate and substrate-surface local environments with temperature stratification while the lid is adjacent but not mechanically contacted during substrate movement. The dependent claim refinements further add a vapor-generated third local environment, a relative humidity constraint, an immersion-fluid optical imaging objective across internal and external regions, and rotatable substrate motion with partial vacuum effects produced by bulk fluid motion between the chamber and the lid.

Stated Advantages

Documented Applications